度普利尤单抗治疗儿童哮喘时肺功能对哮喘加重率的影响：航行研究
Impact of Lung Function on Asthma Exacerbation Rates in Children Treated with Dupilumab: The VOYAGE Study.
作者信息
Guilbert Theresa W, Murphy Kevin R, Hamelmann Eckard, Ross Kristie R, Gupta Atul, Fiocchi Alessandro, Xia Changming, Gall Rebecca, Ledanois Olivier, Radwan Amr, Jacob-Nara Juby A, Rowe Paul J, Deniz Yamo
机构信息
Cincinnati Children's Hospital and University of Cincinnati, Cincinnati, OH, USA.
Boys Town National Research Hospital, Omaha, NE, USA.
出版信息
J Asthma Allergy. 2024 Feb 8;17:81-87. doi: 10.2147/JAA.S425101. eCollection 2024.
BACKGROUND
Severe, uncontrolled asthma and asthma exacerbations in children are associated with abnormal lung function and airway development, and increased risk of chronic obstructive lung disease in adulthood. The rationale for this post hoc analysis was to explore the relationship between changes in asthma exacerbation rates and lung function in children treated with dupilumab.
METHODS
This post hoc analysis included children aged 6 to 11 years with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb) who received dupilumab or placebo in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). Endpoints were the proportion of patients achieving clinically meaningful improvements (≥5% or ≥10%) in pre-bronchodilator percent-predicted forced expiratory volume in 1 second (ppFEV) by Week 12, annualized severe asthma exacerbation rates from Week 12-52, and mean change from baseline in ppFEV to Week 12.
RESULTS
At Week 12 of VOYAGE, 141/236 (60%) of children treated with dupilumab and 57/114 (50%) of children receiving placebo showed improvements of ≥5% in ppFEV; 106/236 (45%) children receiving dupilumab and 36/114 (32%) receiving placebo achieved improvements in ppFEV ≥10%. During the Week 12-52 treatment period, dupilumab vs placebo significantly reduced severe exacerbation rates in all subgroups by 52-60% (all <0.05). Dupilumab treatment resulted in rapid and sustained improvements in ppFEV (Week 12 least squares mean difference [95% CI] vs placebo: 3.54 [0.30, 6.78] percentage points; =0.03) in children who achieved improvements of ≥5%.
CONCLUSION
Dupilumab vs placebo significantly improved pre-bronchodilator ppFEV, with a higher proportion of patients achieving a clinically meaningful response at Week 12. Dupilumab also significantly reduced severe exacerbation rates, independent of pre-bronchodilator ppFEV response at Week 12.
TRIAL REGISTRATION
NCT02948959.
背景
儿童严重、未得到控制的哮喘及哮喘急性发作与肺功能和气道发育异常相关，且成年后患慢性阻塞性肺疾病的风险增加。这项事后分析的目的是探讨接受度普利尤单抗治疗的儿童哮喘急性发作率变化与肺功能之间的关系。
方法
这项事后分析纳入了6至11岁未得到控制的中重度2型哮喘（血嗜酸性粒细胞≥150个/μL或呼出一氧化氮分数≥20 ppb）儿童，这些儿童在3期LIBERTY ASTHMA VOYAGE研究（NCT02948959）中接受了度普利尤单抗或安慰剂治疗。观察终点为在第12周时达到临床意义上改善（≥5%或≥10%）的患者比例（以支气管扩张剂前1秒用力呼气容积预测值百分比表示，即ppFEV）、第12周至52周的年化严重哮喘急性发作率，以及第12周时ppFEV相对于基线的平均变化。
结果
在VOYAGE研究的第12周，接受度普利尤单抗治疗的儿童中有141/236（60%）、接受安慰剂治疗的儿童中有57/114（50%）的ppFEV改善≥5%；接受度普利尤单抗治疗的儿童中有106/236（45%）、接受安慰剂治疗的儿童中有36/114（32%）的ppFEV改善≥10%。在第12周至52周的治疗期间，度普利尤单抗与安慰剂相比，在所有亚组中均显著降低严重急性发作率52%-60%（均P<0.05）。度普利尤单抗治疗使ppFEV得到快速且持续的改善（第12周最小二乘均值差异[95%CI]与安慰剂相比：3.54[0.30, 6.78]个百分点；P=0.03），这些儿童的ppFEV改善≥5%。
结论
与安慰剂相比，度普利尤单抗显著改善了支气管扩张剂前的ppFEV，在第12周时有更高比例的患者获得了具有临床意义的反应。度普利尤单抗还显著降低了严重急性发作率，且与第12周时支气管扩张剂前ppFEV的反应无关。
试验注册号
NCT02948959。
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